Acute colonic pseudo-obstruction (ACPO):
The 2020 American Society for Gastrointestinal Endoscopy (ASGE) guideline identifies neostigmine as the pharmacologic agent of choice for ACPO and recommends its use in patients who are not candidates for conservative therapy, who have failed conservative therapy for up to 72 hours, or who are at risk for perforation and have no contraindication to treatment. During administration, continuous cardiac and respiratory monitoring is required, with immediate access to atropine for bradycardia, and glycopyrrolate may be coadministered to reduce hypersalivation and bronchospasm. Contraindications include intestinal or urinary obstruction and hypersensitivity, and relative contraindications include bradycardia, asthma, renal insufficiency, peptic ulcer disease, recent myocardial infarction, and acidosis. A standard dose of 2 mg IV over 3 to 5 minutes is recommended, and in patients who fail an initial dose, are partial responders, or experience recurrence, a second dose has been associated with clinical responses in 40% to 100% of cases. The guideline notes that alternative neostigmine regimens, including subcutaneous administration and continuous intravenous (IV) infusion at 0.4 to 0.8 mg/hour over 24 hours, have been reported to be effective, sometimes with fewer adverse effects. For cases refractory to neostigmine, additional pharmacologic agents described in the guideline include oral pyridostigmine, methylnaltrexone, and traditional prokinetics such as metoclopramide and erythromycin, as well as prucalopride in a reported case of acute refractory pseudo-obstruction, though further evidence is needed before these therapies can be routinely recommended. [1]
Guidelines published by the American Society of Colon and Rectal Surgeons (ASCRS) in 2021 recommend treatment with neostigmine when acute colonic pseudo-obstruction (ACPO) does not resolve with supportive therapy, which is issued as a strong recommendation based on moderate-quality evidence. Neostigmine is generally administered as an IV bolus dose of 2 to 2.5 mg, consistent with the 2 mg IV dose used in the landmark randomized trial by Ponec et al. A prominent meta-analysis reported that a single IV dose of 2 to 5 mg achieved clinical success in 60–94% of patients, with recurrence rates ranging from 0–31% and overall long-term response rates of 69–100%. Studies have also described comparable efficacy and safety with continuous IV infusion, particularly in patients who are refractory to bolus dosing, although continuous infusion may be associated with increased bradycardic events. Tables 1–4 of the guideline summarize the major clinical trials supporting these recommendations. [2]
A review of literature on the safety and effectiveness of neostigmine for the treatment of postoperative ACPO suggests neostigmine as an effective treatment option if patients have failed conservative treatment measures. Data, primarily from observational studies, have found that neostigmine reduced the duration of ACPO compared to conservative treatment alone, improved clinical symptoms, and led to fewer recurrent episodes for patients who failed conservative management. However, its role as first-line therapy for ACPO remained equivocal. Besides commonly described anticholinergic effects from neostigmine, patients should be under close cardiac monitoring for prompt identification of bradycardia, which has been reported to be managed with atropine. The authors have highlighted notable limitations, including the heterogeneity in study populations, use of adjuvant agents, neostigmine regimens, and variety in methodology and measurement of outcomes. A summary of the examined studies can be found in Table 1. [3], [4]
A 2014 meta-analysis included four studies (N= 127 patients) to assess the effectiveness and safety profile of neostigmine in the treatment of patients with ACPO. Only three studies used IV neostigmine (dose range, 2-5 mg) with an administration time ranging from 3 minutes to 12 hours. Acute colonic pseudo-obstruction was resolved in 89.2% (ranging from 84.6 to 95.2%) in the neostigmine group compared to 14.8% (from 0.0 to 45.0%) in the placebo group (NNT= 1; 95% confidence interval [CI], 1 to 2). Abdominal pain (53.1%; odds ratio [OR] 17.4, 95% CI, 5.3 to 57.2) followed by sialorrhoea (31.1%; OR 9.4, 95% CI 3.0 to 29.2) were the most common adverse events reported in the studies. Other less common side effects included vomiting (15.6%) and bradycardia (6.3%). The authors noted that, given the considerable heterogeneity and relatively low power of studies, the role of neostigmine as first-line therapy for ACPO and its optimum dose remains unclear. [5]
Chronic intestinal pseudo-obstruction (CIPO) – adults:
The 2020 British Society of Gastroenterology (BSG) guideline on adult chronic intestinal dysmotility notes that pharmacologic therapy offers limited and variable benefit and should be directed by symptom profile. The guideline emphasizes first eliminating medications that impair motility, especially opioids, anticholinergics, and chronic cyclizine, because these can mimic or worsen pseudo-obstruction. Prokinetic agents may be used on a trial basis, including prucalopride, erythromycin, metoclopramide, and octreotide, though evidence supporting any agent is weak and responses are inconsistent. Octreotide may improve migrating motor complexes in neuropathic dysmotility, while erythromycin predominantly benefits gastric emptying. Additional pharmacologic measures include targeted antibiotics for small intestinal bacterial overgrowth and cautious use of neuropathic pain agents to avoid further slowing motility. Overall, the guideline characterizes drug therapy as adjunctive and modest in effect, best utilized within a multidisciplinary management strategy. [6]
The 2020 review emphasizes that pharmacologic therapy in CIPO is limited by a lack of high-quality evidence, and most available agents provide only partial or symptomatic benefit. The review notes that prokinetic agents such as metoclopramide, domperidone, and erythromycin have been used to stimulate upper gastrointestinal motility, although their efficacy in CIPO is generally modest and often transient. Octreotide is described as beneficial in select neuropathic cases due to its ability to induce migrating motor complexes, whereas anticholinesterase agents such as neostigmine and pyridostigmine may improve intestinal propulsion in some patients, particularly those with neuropathic dysmotility. The review underscores that no pharmacologic therapy has demonstrated consistent, robust improvement across the CIPO population, and that treatment remains largely individualized, with drugs used as adjuncts to nutritional support, decompression strategies, and management of complications such as small intestinal bacterial overgrowth. Overall, the pharmacologic landscape is characterized as limited, variably effective, and supported primarily by small studies and case series. [7]
Pediatric intestinal pseudo-obstruction (PIPO):
The 2018 ESPGHAN/NASPGHAN guideline on PIPO establishes standardized diagnostic criteria and structured management but emphasizes that pharmacologic therapy has virtually no evidence base, with recommendations derived almost entirely from expert consensus and very low-quality evidence (e.g., GRADE D). The guideline distinguishes PIPO from adult CIPO and stresses early referral to expert centers, multidisciplinary evaluation, and optimization of nutrition as the foundation of therapy. For medications, the working group notes that available data consist mainly of anecdotal experience and extrapolation from adult literature, and therefore issues only weak suggestions regarding the selective use of prokinetic agents (for example, to guide therapy when antroduodenal manometry predicts responsiveness) and the cautious use of antibiotics for small-bowel bacterial overgrowth. Drug treatment is framed as adjunctive, with no strong or evidence-based pharmacologic recommendations, and clinical decisions should rely on physiologic testing, symptom profile, and multidisciplinary oversight. [8]
A 2023 survey conducted among the Intestinal Failure (IF) teams within the European Reference Network for rare Inherited and Congenital Anomalies (ERNICA) investigated current diagnostic and management strategies for PIPO. The survey included 11 ERNICA IF centers from 8 countries, each with distinct approaches to managing this rare condition. From April 2020 to June 2022, the survey, comprising 49 closed questions, captured detailed insights into the diagnostic protocols and management practices for PIPO across these centers. The participating centers reported a total of 102 PIPO patients under follow-up, with 78% of these patients dependent on parenteral nutrition (PN). The survey highlighted diverse strategies in the nutritional, medical, and surgical management of PIPO. Nutritional care predominantly prioritized oral feeding, with multidisciplinary teams guiding individualized enteral and PN management. Medical management varied widely, with no prokinetic medications uniformly prescribed across all centers. Surgical strategies included decompressing ileostomy and venting gastrostomy, but the approach to small bowel resection was inconsistent. The findings indicate that while the diagnostic protocols for PIPO generally adhere to international guidelines, considerable variation exists in the management strategies employed by ERNICA IF teams. [9]
The 2022 systematic review provides an updated synthesis of PIPO. In terms of management, the review supports a multidisciplinary approach centered on optimized nutrition and careful use of pharmacologic therapy. Consistent with the ESPGHAN guideline evidence base, it notes that no pharmacologic agent has proven reliably effective, but summarizes emerging pediatric data showing potential benefit from prucalopride, pyridostigmine, and other prokinetics, largely from small case series. It also identifies adjunctive therapies under investigation, including cannabinoids, herbal medicines, fecal microbiota transplantation, and immunotherapy for autoimmune GI dysmotility, while stressing that these remain experimental and require further validation. Intestinal transplantation continues to serve as a life-saving intervention for severe, PN-dependent disease. Overall, the review emphasizes major gaps in evidence and the need for continued research but affirms current consensus-based strategies for diagnosis and management. [10]